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Research & Scholarship

Current Research and Scholarly Interests

Clinical investigations focus on head and neck cancer with a particular interest in combined modality therapy. Through the Stanford University Head and Neck Tumor Board, clinical trials are conducted which involve all aspects of care for patients with head and neck cancer. The clinical research program includes translation of preclinical work performed in the Radiobiology Section at Stanford, new drug development, the development of novel combination therapy, chemoprevention, and the integration of biological response modifiers into combined modality treatment.

As a member of Stanfords Eastern Cooperative Oncology Group trials effort, Dr. Pinto is involved in the implementation and development of a variety of clinical trials at Stanford and the Palo Alto Veterans Affairs Medical Center.

Clinical Trials

RATIONALE: Cyclosporine may help the immune system slow the growth of angioimmunoblastic
T-cell lymphoma.
PURPOSE: This phase II trial is studying how well cyclosporine works in treating patients
with recurrent or refractory angioimmunoblastic T-cell lymphoma.

Weekly Docetaxel, Cisplatin, and Cetuximab (TPC) in Palliative Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN)Not Recruiting

Docetaxel and cetuximab are FDA approved for the treatment of squamous cell carcinoma of the
head and neck. Cisplatin and carboplatin, while not FDA approved for Squamous Cell Carcinoma
of the Head and Neck (SCCHN), have been used as standard of care in patients with SCCHN in
combination with other drugs. This study will determine if weekly cisplatin and docetaxel,
in combination with cetuximab, will be effective in palliative treatment of patients with
squamous cell carcinoma of the head and neck. These drugs will be given intravenously
weekly, repeated 3 of every 4 weeks until evidence of disease progression or unacceptable
adverse events.

Stanford is currently not accepting patients for this trial.For more information, please contact Risa Jiron, 650-736-1598.

RATIONALE: Vaccines made from peptides may make the body build an immune response to kill
tumor cells.
PURPOSE: This randomized phase II trial is studying four different vaccines using melanoma
peptides from cytotoxic T cells and helper T cells to see how well they work in treating
patients with metastatic melanoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Sunil Arani Reddy, (650) 736 - 1234.

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different
ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells
and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy
work in different ways to stop the growth of cancer cells, either by killing the cells or by
stopping them from dividing. Giving rituximab together with combination chemotherapy may
kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving rituximab together with combination
chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large
B-cell non-Hodgkin's lymphoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Lauren Pernicka, (650) 721 - 6977.

The primary objective of this study is to explore the efficacy of BIBW 2992 compared with
cetuximab (Erbitux) in patients with metastatic or recurrent head and neck cancer after
failure of platinum-containing therapy. In addition, the trial aims to clarify the influence
of EGFR genotype on tumor response to the treatment regimens.

Stanford is currently not accepting patients for this trial.For more information, please contact Ruth Lira, (650) 723 - 1367.

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill
them or deliver cancer-killing substances to them without harming normal cells. It is not
yet known which rituximab regimen is more effective in treating indolent non-Hodgkin's
lymphoma.
PURPOSE: This randomized phase III trial is studying two different schedules of rituximab
and comparing them to see how well they work in treating patients with low tumor burden
indolent stage III non-Hodgkin's lymphoma or stage IV non-Hodgkin's lymphoma.

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different
ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells
and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the
growth of cancer cells by blocking blood flow to the cancer. Drugs used in chemotherapy work
in different ways to stop the growth of cancer cells, either by killing the cells or by
stopping them from dividing. Giving bevacizumab together with combination chemotherapy may
kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with several
chemotherapy drugs (combination chemotherapy) works in treating patients with peripheral
T-cell lymphoma or natural killer cell neoplasms.

Stanford is currently not accepting patients for this trial.For more information, please contact Maria Ahern, (650) 725 - 6413.

RATIONALE: Preclinical studies indicate that sorafenib is a potent inhibitor of Raf kinase
in vitro and in vivo, with significant dose-dependent, anti-tumor activity in four different
human tumor types including colon, pancreatic, lung, and ovarian. This activity was
cytostatic in nature and was maintained if dosing was continued. That is, tumor growth is
suspended while the drug is administered but returns to baseline rates when the agent is
withdrawn. Therefore, the optimal schedule will be an uninterrupted one. To assess the
activity of sorafenib in a timely manner and with a meaningful interpretation, a randomized
discontinuation design was adopted in the present trial, conducted in a population who were
potentially sensitive to sorafenib.
PURPOSE: This randomized phase II trial is studying sorafenib to see how well it works
compared to placebo in treating patients with refractory non-small cell lung cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Lisa Zhou, (650) 736 - 4112.

Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck CancerNot Recruiting

This phase I trial studies how well talactoferrin works in treating patients with relapsed
or refractory non-small cell lung cancer (NSCLC) or squamous cell head and neck cancer.
Biological therapies, such as talactoferrin, may stimulate the immune system in different
ways and stop tumor cells from growing

Stanford is currently not accepting patients for this trial.For more information, please contact Melanie San Pedro-Salcedo, (650) 724 - 1388.

Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By SurgeryNot Recruiting

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth.
PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with
locally advanced or metastatic mucosal melanoma or acral melanoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Jennifer Wong, 650-723-1002.

Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck CancerNot Recruiting

The purpose of this research study is to test the safety and effectiveness of palifermin to
determine if weekly doses can be safely administered to reduce the incidence (occurrence
of), duration (length of time) and severity (amount of pain) of oral mucositis (painful
sores in the mouth). Mucositis is a common side effect for patients receiving chemotherapy
(cancer-killing drug) and radiotherapy (cancer-killing x-rays) for the treatment of head and
neck cancer (HNC).

Stanford is currently not accepting patients for this trial.For more information, please contact Rachel Freiberg, (650) 725 - 4777.

Bicalutamide With or Without Akt Inhibitor MK2206 in Treating Patients With Previously Treated Prostate CancerNot Recruiting

This phase II trial studies how well giving bicalutamide with or without Akt inhibitor
MK2206 works in treating patients with previously treated prostate cancer. Androgens can
cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may
lessen the amount of androgens made by the body. Akt inhibitor MK2206 may stop the growth of
tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known
whether bicalutamide is more effective with or without Akt inhibitor MK2206 in treating
prostate cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Preeti Chavan, 650-725-0426.

Chemotherapy With or Without Bevacizumab in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-small Cell Lung Cancer That Was Removed By SurgeryNot Recruiting

This randomized phase III trial studies chemotherapy and bevacizumab to see how well they
work compared to chemotherapy alone in treating patients with stage IB, stage II, or stage
IIIA non-small cell lung cancer that was removed by surgery. Drugs used in chemotherapy work
in different ways to stop the growth of tumor cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Giving more than one drug
(combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as
bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab
also may stop the growth of non-small cell lung cancer by blocking the growth of new blood
vessels necessary for tumor growth. It is not yet known whether chemotherapy is more
effective with or without bevacizumab in treating non-small cell lung cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Maria Pitsiouni, 650-721-6977.

This phase II trial is studying how well giving rituximab together with combination
chemotherapy and 90-Yttrium ibritumomab tiuxetan works in treating patients with stage I or
stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide,
doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so
they stop growing or die. Monoclonal antibodies such as rituximab and yttrium 90-Yttrium
ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive
cancer-killing substances to them without harming normal cells. Combining a monoclonal
antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more
cancer cells.

Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By SurgeryNot Recruiting

This randomized phase III trial studies sunitinib malate to see how well it works compared
to sorafenib tosylate or placebo in treating patients with kidney cancer that has been
removed by surgery. Sunitinib malate and sorafenib tosylate may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to
the tumor. Giving sunitinib malate or sorafenib tosylate after surgery may kill any tumor
cells that remain after surgery. It is not yet known whether sunitinib malate is more
effective than sorafenib tosylate or placebo in treating kidney cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Denise Haas, (650) 736 - 1252.

Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells
from dividing so they stop growing or die. Gefitinib may stop the growth of tumor cells by
blocking the enzymes necessary for their growth. Combining docetaxel with gefitinib may kill
more tumor cells. It is not yet known whether docetaxel is more effective with or without
gefitinib in treating head and neck cancer. This randomized phase III trial is studying
docetaxel and gefitinib to see how well they work compared to docetaxel alone in treating
patients with metastatic or locally recurrent head and neck cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Dimitrios Colevas, (650) 724 - 9707.

Cisplatin and ZD1839 + Re-Irradiation in Recurrent Squamous Cell Cancer of the Head and NeckNot Recruiting

To determine safety profile of the epidermal growth factor receptor (EGFR) antagonist,
ZD1839 in combination with cisplatin and radiation therapy in patients with local-regional
recurrent squamous cell cancer of the head and neck.
To study the effects of ZD1839 combined with either cisplatin or radiotherapy on signal
transduction pathway gene expression in tumor cells in patients with local-regional
recurrent squamous cell cancer of the head and neck using micro array analysis from tumor
samples taken at the time of relapse and during treatment.

Stanford is currently not accepting patients for this trial.For more information, please contact Priscilla Wong, (650) 725 - 4777.

A Study of MEHD7945A Versus Cetuximab in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of The Head And NeckNot Recruiting

This phase II, open-label, randomized study will evaluate the efficacy and safety of
MEHD7945A versus cetuximab in patients with recurrent/metastatic squamous cell carcinoma of
the head and neck who have progressed during or following platinum-based chemotherapy.
Patients will be randomized to receive either MEHD7945A 1100 mg intravenously (iv) every 2
weeks or cetuximab 400 mg/m2 iv loading dose followed by 250 mg/m2 iv weekly. Patients
treated with cetuximab (Arm B) may cross-over to MEHD7945A (Arm A) upon central confirmation
of progressive disease and upon meeting eligibility criteria. Anticipated time on study
treatment is until disease progression or intolerable toxicity occurs.

Stanford is currently not accepting patients for this trial.For more information, please contact Ruth Lira, (650) 723 - 1367.

Carboplatin and Paclitaxel With or Without Sorafenib Tosylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by SurgeryNot Recruiting

This randomized phase III trial studies carboplatin, paclitaxel, and sorafenib tosylate to
see how well they work compared to carboplatin and paclitaxel in treating patients with
stage III or stage IV melanoma that cannot be removed by surgery. Drugs used in
chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth
of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib
tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell
growth and by blocking blood flow to the tumor. It is not yet known whether giving
carboplatin and paclitaxel together with sorafenib tosylate is more effective than
carboplatin and paclitaxel in treating melanoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Sunil Reddy, (650) 736 - 1234.

Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid LeukemiaNot Recruiting

This randomized phase II trial studies azacitidine with or without entinostat to see how
well they work compared to azacitidine alone in treating patients with myelodysplastic
syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia. Drugs used in
chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Entinostat may stop the growth of cancer cells by blocking some of the enzymes
needed for cell growth. Giving azacitidine together with entinostat may work better in
treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute
myeloid leukemia.

Stanford is currently not accepting patients for this trial.For more information, please contact Mai Tran, (650) 723 - 8594.

This phase II trial is studying how well sorafenib works in treating patients with recurrent
diffuse large B-cell non-Hodgkin's lymphoma. Sorafenib may stop the growth of cancer cells
by blocking some of the enzymes needed for cell growth and by blocking blood flow to the
tumor.

Stanford is currently not accepting patients for this trial.For more information, please contact Sarah Daadi, (650) 725 - 6456.

Phase 2 Study of GSK1363089 (Formerly XL880) in Adults With Squamous Cell Cancer of the Head and NeckNot Recruiting

This study is being conducted to determine the best confirmed response rate, safety, and
tolerability of GSK1363089 treatment in adult subjects with squamous cell carcinoma of the
head and neck (SCCHN). GSK1363089 is a new chemical entity that inhibits multiple receptor
tyrosine kinases (RTKs) with growth-promoting and angiogenic properties. The primary targets
of GSK1363089 are the HGF and vascular endothelial growth factor (VEGF) RTK families (eg,
MET, VEGFR2/kinase insert domain receptor [KDR]). Since MET overexpression has been
associated with poorer prognosis and MET tyrosine kinase mutations have been reported in
SCCHN, inhibition of MET receptor and VEGFR2/KDR activation by agents such as GSK1363089 may
be of therapeutic benefit in this patient population.

Stanford is currently not accepting patients for this trial.For more information, please contact Ruth Lira, (650) 723 - 1367.

Compassionate Use Trial for Unresectable Melanoma With IpilimumabNot Recruiting

The primary objective of the study is to provide treatment with Ipilimumab to subjects who
have serious or immediately life-threatening unresectable Stage III or Stage IV melanoma,
who have no alternative treatment options, and whose physicians believe, based upon
available data on benefit and risk, that it is appropriate to administer Ipilimumab at a
dose of 3 mg/kg induction (with re-induction, if eligible), or for eligible subjects
previously enrolled in Ipilimumab studies CA184-042, CA184-078, CA184-087, MDX010-16, or
MDX010-20.

Stanford is currently not accepting patients for this trial.For more information, please contact Sunil Arani Reddy, (650) 736 - 1234.

A Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in Treating Patients With Operable Head and Neck CancerNot Recruiting

IRX-2 is designed to activate your own body's immune system so that it can better fight the
invasion of head and neck cancer. In pre-clinical studies, IRX-2 has been shown to activate
a number of different cells of the immune system.
IRX-2 was previously tested in a study of 13 patients with advanced head and neck cancer who
had been previously treated and failed chemotherapy and/or radiation therapy. The trials
were specifically designed to test the safety of IRX-2. Researchers found that IRX-2 did not
appear to have major side effects. Also, the researchers believed that further study in less
advanced head and neck cancer patients could be useful in obtaining more data on the safety
of IRX-2 as well as data on possible effects on tumors and on patient survival.

Stanford is currently not accepting patients for this trial.For more information, please contact Ruth Lira, (650) 723 - 1367.

We propose to combine lapatinib with RT alone in patients with locally advanced head and
neck cancer who cannot tolerate chemotherapy. The main objective of the study is to
determine the efficacy of combining concurrent radiation and lapatinib in terms of
time-to-progression (TTP) in this group of patients. In addition, we will determine the
2-year locoregional control rate (LRC), progression-free survival (PFS) and overall survival
(OS) in these patients. We will also evaluate the profile and frequency of late toxicity,
specifically mucosal and dermatologic toxicity, of the combination of lapatinib and RT in
patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Stanford is currently not accepting patients for this trial.For more information, please contact Brian Khong, (650) 725 - 4777.

The purpose of this research study is to evaluate the progression-free survival (PFS) with
XL184 as compared with placebo (an inactive substance) in subjects with unresectable,
locally advanced, or metastatic medullary thyroid cancer (MTC). Subjects will be randomized
to receive XL184 or placebo in a 2:1 ratio. XL184 is an investigational drug that inhibits
VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.
The Clinical Steering Committee for this study, comprised of study doctors who specialize in
medullary thyroid cancer, has provided guidance regarding the design of the study. The
committee includes: Douglas Ball, MD, Barry Nelkin, PhD, Martin Schlumberger, MD and Steven
Sherman, MD.

Stanford is currently not accepting patients for this trial.For more information, please contact Ruth Lira, (650) 723 - 1367.

Identification of Secreted Markers for Tumor Hypoxia in Patients With Head and Neck or Lung CancersRecruiting

The purpose of this study is to identify and confirm new blood and tissue markers for
prognosis and tumor hypoxia. Tumor hypoxia, or the condition of low oxygen in the tumor, has
been shown to increase the risk of tumor spread and enhance tumor resistance to the standard
treatment of radiation and chemotherapy in head and neck and lung cancers. We have recently
identified several proteins or markers in the blood and in tumors (including osteopontin,
lysyl oxidase, macrophage inhibiting factor and proteomic technology) in the laboratory that
may be able to identify tumors with low oxygen levels or more aggressive behaving tumors.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor
cells. Combining chemotherapy with radiation therapy may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by
radiation therapy and chemotherapy in treating patients who have stage III or stage IV
cancer of the larynx or stage III or stage IV cancer of the oropharynx.

Stanford is currently not accepting patients for this trial.For more information, please contact Nancy Mori, (650) 724 - 0201.

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different
ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different
ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
help kill them or carry tumor-killing substances to them. Radiation therapy uses high energy
x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with
radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how
well they work when followed by cetuximab and two different doses of intensity-modulated
radiation therapy in treating patients with HPV-associated stage III or stage IV cancer of
the oropharynx that can be removed by surgery.

Stanford is currently not accepting patients for this trial.For more information, please contact Lauren Pernicka, (650) 721 - 6977.

Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck CancerNot Recruiting

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in
chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells,
either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor
cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can
block tumor growth in different ways. Some block the ability of tumor cells to grow and
spread. Others find tumor cells and help kill them or carry tumor-killing substances to
them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor
cells. It is not yet known whether radiation therapy and cisplatin are more effective with
or without cetuximab in treating head and neck cancer.
PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and
cetuximab to see how well they work compared to radiation therapy and cisplatin in treating
patients with stage III or stage IV head and neck cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Trevor Elizabeth Krakow, (650) 725 - 4777.

A Longitudinal Study of Plasma EBV DNA in Nasopharyngeal Carcinoma From Both Endemic and Non-Endemic Patient PopulationsNot Recruiting

1. To determine the prognostic implication of plasma Epstein-Bar Virus (EBV) DNA
concentrations, as measured by quantitative polymerase chain reaction (PCR) in patients
with nasopharyngeal carcinoma (NPC).
2. To relate pretreatment plasma EBV DNA concentration to WHO classification of these
tumors both in endemic and non-endemic areas.
3. To determine whether pretreatment plasma EBV DNA can serve as a prognostic factor for
both endemic and non-endemic patient populations.

Stanford is currently not accepting patients for this trial.For more information, please contact Quynh-Thu Le, 650-498-6184.

Doxorubicin Hydrochloride, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast CancerNot Recruiting

This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and
paclitaxel to see how well they work with or without bevacizumab in treating patients with
cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not
spread to the lymph nodes but is at high risk for returning (high-risk, lymph node-negative
breast cancer). Drugs used in chemotherapy, such as doxorubicin hydrochloride,
cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of
tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by
blocking blood flow to the tumor. Giving chemotherapy after surgery may kill any tumor cells
that remain after surgery and help prevent the tumor from returning. It is not yet known
whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are more effective with
or without bevacizumab.

Stanford is currently not accepting patients for this trial.For more information, please contact Pei-Jen Chang, (650) 725 - 0866.

Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by SurgeryNot Recruiting

This randomized phase III trial studies ipilimumab to see how well it works compared to
high-dose interferon alfa-2b in treating patients with high-risk stage III-IV melanoma that
has been removed by surgery. Monoclonal antibodies, such as ipilimumab, may interfere with
the ability of tumor cells to grow and spread. Interferon alfa-2b may interfere with the
growth of tumor cells and slow the growth of melanoma and other cancers. It is not yet known
whether ipilimumab is more effective than interferon alfa-2b in treating patients with
melanoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Preeti Chavan, 650-725-0426.

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. It is not yet
known whether treatment with interferon alfa is more effective than observation alone for
stage II or stage III melanoma that has been completely removed surgically.
PURPOSE: This randomized phase III trial is studying high dose interferon alfa to see how
well it works compared to observation only in treating patients with stage II or stage III
melanoma that has been completely removed by surgery.

Stanford is currently not accepting patients for this trial.For more information, please contact Sunil Arani Reddy, (650) 736 - 1234.

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the
development or recurrence of cancer. It is not yet known if selenium is effective in
preventing the growth of new tumors in patients with previously resected non-small cell lung
cancer.
PURPOSE: This randomized phase III trial is studying selenium to see how well it works
compared to a placebo in preventing the development of second primary lung tumors in
patients who have undergone surgery to remove stage I non-small cell lung cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Nancy Mori, (650) 724 - 0201.

Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon CancerNot Recruiting

This randomized phase III trial studies oxaliplatin, leucovorin calcium, fluorouracil, and
bevacizumab to see how well they work compared to oxaliplatin, leucovorin calcium, and
fluorouracil in treating patients who have undergone surgery for stage II colon cancer.
Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work
in different ways to stop the growth of tumor cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such
as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not
yet known whether giving combination chemotherapy together with bevacizumab is more
effective than combination chemotherapy alone in treating colon cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Nancy Mori, (650) 724 - 0201.

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from
dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and
either kill them or deliver radioactive tumor-killing substances to them without harming
normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy
regimen is more effective in treating non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies
given together with combination chemotherapy to see how well they work in treating patients
with newly-diagnosed non-Hodgkin's lymphoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Lauren Pernicka, (650) 721 - 6977.

This phase II trial is studying how well giving rituximab together with combination
chemotherapy and bortezomib works in treating patients with untreated mantle cell lymphoma.
Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some
block the ability of cancer cells to grow and spread. Others find cancer cells and help kill
them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as
cyclophosphamide, doxorubicin, vincristine, and dexamethasone, work in different ways to
stop the growth of cancer cells, either by killing the cells or stopping them from dividing.
Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for
cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill
more cancer cells.
Treatment consists of six agents: bortezomib (Vc), rituximab (R), cyclophosphamide (C),
vincristine (V), doxorubicin (A), and dexamethasone (D) (VcR-CVAD).

Stanford is currently not accepting patients for this trial.For more information, please contact Lauren Pernicka, (650) 721 - 6977.

Radiation Therapy With or Without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck CancerNot Recruiting

RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to
help focus thin beams of radiation directly on the tumor, and giving radiation therapy in
higher doses over a shorter period of time, may kill more tumor cells and have fewer side
effects. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways.
Some block the ability of tumor cells to grow and spread. Others find tumor cells and help
kill them or carry tumor-killing substances to them. It is not yet known whether radiation
therapy is more effective when given alone or together with cetuximab in treating patients
with head and neck cancer that has been removed by surgery.
PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it
works compared with radiation therapy given together with cetuximab in treating patients who
have undergone surgery for locally advanced head and neck cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Alice Banh, 650-723-1423.

Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by SurgeryNot Recruiting

This randomized phase II trial is studying how well giving ipilimumab with or without
sargramostim (GM-CSF) works in treating patients with stage III or stage IV melanoma that
cannot be removed by surgery. Ipilimumab works by activating the patient's immune system to
fight cancer. Colony-stimulating factors, such as sargramostim, may increase the number of
immune cells found in bone marrow or peripheral blood and may help the immune system recover
from the side effects of treatment. It is not yet known whether giving ipilimumab together
with sargramostim is more effective than ipilimumab alone in treating melanoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Vani Jain, (650) 725 - 5459.

Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell CarcinomaNot Recruiting

This randomized phase III trial studies chemotherapy to see how well it works with or
without bevacizumab in treating patients with head and neck squamous cell carcinoma that has
come back (recurrent) or that has spread to other parts of the body (metastatic). Drugs used
in chemotherapy, such as docetaxel, cisplatin, carboplatin, and fluorouracil, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as
bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab
may also make tumor cells more sensitive to chemotherapy and stop the growth of head and
neck cancer by blocking blood flow to the tumor. It is not yet known whether combination
chemotherapy is more effective when given with or without bevacizumab in treating patients
with head and neck squamous cell carcinoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Jennifer Wong, 650-723-1002.

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different
ways. Some find cancer cells and kill them or carry cancer-killing substances to them.
Others interfere with the ability of cancer cells to grow and spread. Drugs used in
chemotherapy, such as methotrexate, leucovorin, vincristine, procarbazine, dexamethasone,
and cytarabine, work in different ways to stop the growth of cancer cells, either by killing
the cells or by stopping them from dividing. Giving rituximab together with combination
chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving rituximab together with combination
chemotherapy works in treating patients with primary central nervous system (CNS) lymphoma.

Stanford is currently not accepting patients for this trial.For more information, please contact Lauren Pernicka, (650) 721 - 6977.

Abstract

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

Abstract

To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease.We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed.The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR?pCR, and cPR?pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR?pCR, and cPR?pPR groups were 53%, 75%, and 42%, respectively (p = 0.04).In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.

Abstract

Neoadjuvant chemoradiotherapy followed by surgery is the primary treatment option for patients with locally advanced esophageal cancer. This multicenter phase I trial examined intratumoral injection of TNFerade biologic, an adenoviral vector that expresses the human tumor necrosis factor-? gene, with chemoradiotherapy in locally advanced esophageal cancer.To assess pathologic complete response (pCR), time to disease progression, progression-free survival, survival, and safety and tolerance in patients treated with preoperative chemoradiation combined with endoscopy or EUS-guided intratumoral injection of TNFerade biologic.Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 × 10(8) to 4 × 10(11) particle units (PU), were given in combination with cisplatin 75 mg/m(2) and intravenous 5-fluorouracil 1000 mg/m(2)/d for 96 hours on days 1 and 29, and concurrent radiation therapy to 45 Gy. Surgery was performed 9 to 15 weeks after treatment.U.S. multicenter study.Patients with stage II and III esophageal cancer were enrolled.Primary outcome measures were safety, feasibility, tolerability, and rate of pCR. Secondary outcome measures were overall survival (OS) and disease-free survival.Twenty-four patients with a median age of 61 years were enrolled; 88% of the patients were men, 21% were stage II, and 79% were stage III. Six (29%) had a pCR, observed among 21 patients (20 who underwent esophagectomy and 1 at autopsy). Dose-limiting toxicities were not observed. The most frequent potentially related adverse events were fatigue (54%), fever (38%), nausea (29%), vomiting (21%), esophagitis (21%), and chills (21%). At the top dose of 4 × 10(11) PU, thromboembolic events developed in 5 of 8 patients. The median OS was 47.8 months. The 3- and 5-year OS rates and disease-free survival rates were 54% and 41% and 38% and 38%, respectively.We included primarily adenocarcinoma.Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 × 10(10) PU and is associated with long survival. This regimen warrants additional studies.

Abstract

To investigate in vivo(1)H magnetic resonance spectroscopy imaging of lactate for assessing tumor hypoxia in head and neck cancers and to determine its utility in predicting the response and outcomes.Volume-localized lactate-edited (1)H magnetic resonance spectroscopy at 1.5 T was performed in vivo on involved neck nodes and control subcutaneous tissues in 36 patients with Stage IV head and neck cancer. The signal intensities (SIs) of lactate, choline, and creatine and the choline/creatine ratio were measured. The tumor partial pressure of oxygen (pO(2)) was obtained in the same lymph node before MRS. Patients were treated with either two cycles of induction chemotherapy (tirapazamine, cisplatin, 5-fluorouracil) followed by simultaneous chemoradiotherapy or the same regimen without tirapazamine. The lactate SI and the choline/creatine ratio correlated with the tumor pO(2), nodal response, and locoregional control.The lactate SI was greater for the involved nodes (median, 0.25) than for the subcutaneous tissue (median, 0.04; p = 0.07). No significant correlation was found between the lactate SI and tumor pO(2) (mean, 0.46 +/- 0.10 for hypoxic nodes [pO(2) < or =10 mm Hg, n = 15] vs. 0.36 +/- 0.07 for nonhypoxic nodes [pO(2) >10 mm Hg, n = 21], p = 0.44). A significant correlation was found between the choline/creatine ratios and tumor pO(2) (mean, 2.74 +/- 0.34 for hypoxic nodes vs. 1.78 +/- 0.31 for nonhypoxic nodes, p = 0.02). No correlation was found between the lactate SI and the complete nodal response (p = 0.52) or locoregional control rates.The lactate SI did not correlate with tumor pO(2), treatment response, or locoregional control. Additional research is needed to refine this technique.

Abstract

To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

Abstract

Taxane-based concurrent chemoradiotherapy (CCR) for head and neck cancers has proven to have a favorable toxicity profile compared with cisplatin and radiation. This phase II multi-institutional trial evaluates taxane-based induction chemotherapy followed by CCR for organ preservation in resectable stage III/IVA and IVB larynx and oropharynx (OP) cancer patients.Eligibility required resectable stage T2N+, or T3-T4N0-3M0 biopsy-proven squamous carcinoma, age at least 18 years, PS 0 to 2, good organ function, and no prior chemotherapy or radiation. Treatment was induction paclitaxel 175 mg/m(2) and carboplatin area under the concentration-time curve (AUC) 6 for two cycles every 21 days followed by concurrent paclitaxel 30 mg/m(2) every 7 days with 70 Gy if no evidence of tumor progression. Weekly erythropoietin alpha 40 kU was used for suboptimal hemoglobin (< 14 gm/dL men, < 13 gm/dL women). The primary end point was organ preservation (freedom from primary site salvage surgery or primary tumor recurrence).One hundred five of 111 patients (36 larynx, 69 OP) were eligible. Median follow-up was 36.7 months. Ninety-four percent received full-dose radiotherapy and 91% received at least five cycles of concurrent paclitaxel. No patient progressed while receiving chemotherapy. Organ preservation was 81% at 2 years after completion of therapy (larynx 74%, OP 84%). Thirteen patients required primary-site salvage surgery (seven larynx, six OP), and six of these have progressed and died (three larynx, three OP). Thirteen patients developed distant metastases (seven larynx, six OP; P = .02) and 10 of 36 larynx and 11 of 69 OP patients have died as a result of their disease. Two-year survival is 76% (63% larynx v 83% OP).A high organ preservation rate was obtained with this regimen for OP but not for larynx patients. Toxicity was low, and induction chemotherapy did not preclude delivery of concurrent chemoradiotherapy.

Abstract

18F-FDG PET/CT has rapidly become a widely used imaging modality for evaluating a variety of malignancies, including squamous cell carcinoma of the head and neck and thyroid cancer. Using both published data and the multidisciplinary experience at our institution, we provide a practical set of guidelines and algorithms for the use of 18F-FDG PET/CT in the evaluation and management of head and neck cancer and thyroid cancer.

Abstract

To confirm the relationship between plasma osteopontin (OPN) levels and treatment outcomes in head and neck squamous cell carcinoma (HNSCC) patients in an expanded study.One hundred forty patients with newly diagnosed HNSCC were enrolled onto this study, 54 previously reported and 86 new patients. Pretreatment plasma OPN levels were assessed in all patients by an enzyme-linked immunosorbent assay method. OPN levels were correlated to treatment outcomes in the new group of patients. Detailed analyses were also performed on the relationship between OPN and tumor control rate, event-free survival (EFS), and postrelapse survival for the entire group.Using a previously defined cut off point of 450 ng/mL, there was a significant correlation between OPN and freedom-from-relapse (P = .047), overall survival (P = .019), and EFS (P = .023) in the new, independent patient cohort (n = 86). Sequence of event analyses using the entire group (N = 140) revealed that OPN was an independent prognostic factor for initial tumor control, EFS in those who have achieved tumor control, and postrelapse survival.In this expanded study, we were able to replicate the prognostic significance of OPN using a predefined cut off point in an independent patient group and demonstrated that plasma OPN is an independent prognostic marker for HNSCC.

Abstract

Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site.The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy +/- chemotherapy.No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group.Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC.

Abstract

The objective of this article was to report the results from a randomized trial that evaluated the efficacy and toxicity of adding tirapazamine (TPZ) to chemoradiotherapy in the treatment of patients with head and neck squamous cell carcinomas (HNSCC).Sixty-two patients with lymph node-positive, resectable, TNM Stage IV HNSCC were randomized to receive either 2 cycles of induction chemotherapy (TPZ, cisplatin, and 5-fluorouracil [5-FU]) followed by simultaneous chemoradiotherapy (TPZ, cisplatin, and 5-FU) or to receive the same regimen without TPZ. Patients who did not achieve a complete response at 50 Grays underwent surgical treatment. Stratification factors for randomization included tumor site, TNM stage, and median tumor oxygen tension. The primary endpoint was complete lymph node response.The addition of TPZ resulted in increased hematologic toxicity. There was 1 treatment-related death from induction chemotherapy. The complete clinical and pathologic response rate in the lymph nodes was 90% and 74% for the standard treatment arm and the TPZ arm, respectively (P = .08) and 89% and 90% at the primary site in the respective treatment arms (P = .71). The 5-year overall survival rate was 59%, the cause-specific survival rate was 68%, the rate of freedom from recurrence was 69%, and the locoregional control rate was 77% for the entire group. There was no difference with regard to any of the outcome parameters between the 2 treatment arms. The significant long-term toxicity rate also was found to be similar between the 2 arms.The addition of TPZ increased hematologic toxicity but did not improve outcomes in patients with resectable, Stage IV HNSCC using the protocol administered this small randomized study. The combination of induction and simultaneous chemoradiotherapy resulted in excellent survival in these patients.

Abstract

Malignant tumors of the salivary glands make up approximately 5% of head and neck cancers. The Eastern Cooperative Oncology Group (ECOG) initiated a phase II evaluation of paclitaxel in patients with locally recurrent or metastatic salivary gland malignancies.Chemo-naive patients with histologically confirmed recurrent or metastatic carcinoma of salivary gland origin (mucoepidermoid, adenocarcinoma, or adenoid cystic) were eligible. Patients were treated with paclitaxel, 200 mg/m(2) IV, every 21 days for a minimum of four cycles.Forty-five patients were treated. Eight partial responses were seen among the 31 patients with mucoepidermoid or adenocarcinoma histologic findings for a response rate of 26%. No responses were seen in the adenoid cystic carcinoma group. No significant difference in overall survival was found among these three histologic subgroups.Paclitaxel demonstrates moderate activity in salivary gland tumors of mucoepidermoid and adenocarcinoma histology. The poor response rate in adenoid cystic carcinoma is consistent with prior reports in this chemoresistant histologic subtype.

Abstract

To determine the diagnostic accuracy and the ideal timing of fluoro-fluorodeoxyglucose positron-emission tomography (PET) in the posttreatment surveillance of head and neck mucosal squamous cell carcinoma (HNSCC).Retrospective chart review.Our sample includes 103 adult patients with 118 posttreatment PET scans who had undergone treatment for HNSCC. We correlated PET results with surgical pathology and clinical outcome in the subsequent 6 months.For the detection of locoregional persistent or recurrent HNSCC, PET scans had a sensitivity of 82%, specificity of 92%, positive predictive value (PPV) of 64%, negative predictive value (NPV) of 97%, and overall accuracy of 90%. For the detection of distant metastases, PET scans had a sensitivity of 89%, specificity of 97%, PPV of 85%, NPV of 98%, and overall accuracy of 96%. PET scans of the head and neck region performed greater than 1 month after the completion of radiation compared with scans performed within 1 month had a significantly higher sensitivity of 95% versus 55% (P < .01) and NPV of 99% versus 90% (P < .01).PET is effective in detecting distant metastases in the posttreatment surveillance for HNSCC patients. A negative PET is highly reliable for all sites. However, a positive PET in the head and neck region is unreliable because of a high false-positivity rate. PET of the head and neck region has a statistically significant risk of a false-negative reading when performed within 1 month of radiation.

Abstract

The optimal surgical procedure for the neck in patients with squamous head and neck cancers is controversial. Selective neck dissections have replaced modified radical neck dissections as the procedure of choice for the clinically negative (N0) neck and are now being considered for patients with early-stage neck disease. We report the long-term local recurrence rates in 100 consecutive patients undergoing a radical or modified radical neck dissection for clinically positive (N+) and N0 neck disease and review comprehensively the literature reporting and comparing regional control rates for both neck dissection types.The clinical records of 100 consecutive patients who underwent a comprehensive neck dissection (levels I-V) for squamous head and neck cancers with a minimum of a 2-year follow-up were retrospectively reviewed for primary site of disease, clinical and pathologic neck status, histopathologic grade, neck dissection type, and the site and time of recurrence.Complete data were available for 97 patients on whom 99 neck dissections were performed. Three patients died from unknown causes. Seventy-six patients with N+ disease underwent a therapeutic neck dissection, while 24 patients with clinically N0 disease underwent an elective dissection. The overall neck recurrence rate in patients with controlled primary disease was 7%. The neck or regional failure rate for patients completing the recommended adjuvant radiotherapy was 4%. Six (25%) of 24 patients with clinically N0 disease had occult metastases. The recurrence rate for this group was 4%.Further study is needed to determine the optimal surgical management of the N0 and limited N+ neck.

Abstract

In a single-institution, double-blind, prospective, randomized trial, we determined whether oral aloe vera gel can reduce radiation-induced mucositis in head-and-neck cancer patients.We randomized 58 head-and-neck cancer patients between oral aloe vera and placebo. To be included in this Phase II protocol, patients had to be treated with radiotherapy with curative intent at Stanford University between February 1999 and March 2002. We examined patients biweekly for mucositis at 15 head-and-neck subsites and administered quality-of-life questionnaires.Patients in the aloe and placebo groups were statistically identical in baseline characteristics. By the end of treatment, the two groups were also statistically identical in maximal grade of toxicity, duration of Grade 2 or worse mucositis, quality-of-life scores, percentage of weight loss, use of pain medications, hydration requirement, oral infections, and prolonged radiation breaks.In our randomized study, oral aloe vera was not a beneficial adjunct to head-and-neck radiotherapy. The mean quality-of-life scores were greater in the aloe vera group, but the differences were not statistically significant. Oral aloe vera did not improve tolerance to head-and-neck radiotherapy, decrease mucositis, reduce soreness, or otherwise improve patient well-being.

Abstract

Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control.Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy.At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension.STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.

Abstract

To compare the Eppendorf PO2 histograph and the alkaline comet assay as methods of measuring tumor hypoxia in patients with head-and-neck squamous cell carcinomas.As part of a larger clinical trial, 65 patients with head-and-neck squamous cell carcinoma nodal metastasis underwent tumor oxygenation measurements with Eppendorf PO2 histographs and comet assays, performed on fine-needle aspirates at 1 and 2 min after 5 Gy. Fifty-four patients had sufficient tumor cells for comet analysis at 1 min and 26 at both 1 and 2 min. Individual cells were examined for DNA single-strand breaks by alkaline gel electrophoresis, and the distribution of values was quantified using median tail moment (MTM). Nonirradiated tumor cells from pretreatment fine-needle aspirates received 5 Gy in vitro to establish the oxygenated response.There was a significant correlation between the 1- and 2-min MTM (slope = 0.77 +/- 0.03). There was no relationship between DNA damage in tumor cells irradiated in vitro and in vivo. No correlation was found between Eppendorf PO2 measurements and comet MTM. There was a statistically significant correlation between the treatment response in the node studied and comet MTMs, whereas no correlation was observed between treatment response and Eppendorf measurements.Comet assays are reproducible, as shown by biopsies at 1 and 2 min. Intertumor variation in the MTM is not a result of intrinsic radiosensitivity but of tumor hypoxia. There was no correlation between Eppendorf PO2 measurements and comet MTM. Comet assays were better than Eppendorf in predicting treatment response as an end point for short-term outcome. Longer follow-up is needed to determine the role of the comet assay as a predictor for locoregional tumor control and survivals.

Abstract

Tumor hypoxia modifies treatment efficacy and promotes tumor progression. Here, we investigated the relationship between osteopontin (OPN), tumor pO(2), and prognosis in patients with head and neck squamous cell carcinomas (HNSCC).We performed linear discriminant analysis, a machine learning algorithm, on the NCI-60 cancer cell line microarray expression database to identify a gene profile that best distinguish cell lines with high Von-Hippel Lindau (VHL) gene expression, an important regulator of hypoxia-related genes, from those with low expression. Plasma OPN levels in 15 volunteers, 31 VHL patients, and 54 HNSCC patients were quantitatively measured by ELISA. The relationships between plasma OPN levels, tumor pO(2) as measured by the Eppendorf microelectrode, freedom from relapse (FFR), and survival in HNSCC patients were evaluated.Microarray analysis indicated that OPN gene expression inversely correlated with that of VHL. These findings were confirmed by Northern blot analysis. ELISA studies and Western blot in a HNSCC cell line demonstrated that hypoxia exposure resulted in increased OPN secretion. Patients with VHL syndrome had significantly higher plasma OPN levels than healthy volunteers. Plasma OPN level inversely correlated with tumor pO(2) (P = 0.003, r = -0.42). OPN levels correlated with clinical outcomes. The 1-year FFR and survival rates were 80 and 100%, respectively, for patients with OPN levels 450 ng/ml (P = 0.002 and 0.0005). Multivariate analysis revealed that OPN was an independent predictor for FFR and survival.Plasma OPN levels appeared to correlate with tumor hypoxia in HNSCC patients and may serve as noninvasive tests to identify patients at high risk for tumor recurrence.

Abstract

The alkaline comet assay is a microelectrophoretic technique for detecting single-strand DNA breaks, and may be used as an indirect measure of hypoxia by determining the radiation sensitivity of individual cells.To assess the ability of the comet assay to estimate the rate of DNA repair after irradiation in patients with head and neck cancer.The comet assay was used to evaluate DNA damage in fine-needle aspirates of lymph nodes containing metastatic squamous cell carcinoma in patients with head and neck cancer 1, 2, and 3 minutes after treatment with 500 rad (5 Gy) of irradiation. The amount of DNA damage (measured as the "tail moment" of the comet) is proportional to the number of DNA single-strand breaks after irradiation, which in turn depends on the oxygen concentration in each cell.The mean +/- SD of the median tail moment of the 1-minute postirradiation comets was 29.4 +/- 14.2 (n = 27). After 2 minutes, the mean median tail moment decreased to 25.4 +/- 13.6 (n = 25), representing a mean decrease of 11.9% in those patients with both 1- and 2-minute comet assays. Assuming a linear rate of repair, this decrease in DNA damage corresponds to a repair half-life of 4.2 minutes. A 3-minute assay was also performed on samples from a smaller number of patients (n = 9), with a mean value not significantly different from that of the 2-minute assay of the samples from this group.The comet assay is a promising tool for evaluating radiation sensitivity in individual cells. The rate of DNA repair early after irradiation is consistent with data in the literature.

Abstract

This paper describes the ECOG-NMA Minority Accrual Initiative to assure minority participation in cancer clinical trials.Focus groups were held to identify physician-reported barriers to the enrollment of minority patients in Cleveland, OH, Indianapolis, IN, Santa Clara County, CA, and Philadelphia, PA. Community physicians affiliated with the National Medical Association (NMA), and Eastern Cooperative Oncology Group (ECOG) investigators participated in the focus groups. A four-step process consisting of focus group workshops were conducted to (i) identify barriers, (ii) develop potential solutions to the barriers, (iii) define solutions to barriers involving specific clinical trials, and (iv) implement the solutions.Focus group participants identified physician lack of information, patient fears and suspicion, the fear of losing patients, and distrust of the health care system as the major barriers to enrollment of African Americans. We found significant differences between community physicians and cancer program physicians in several areas. Community physicians emphasized personal contacts to address the lack of information and to overcome patient fears and suspicions, while the cancer program physicians emphasized printed materials. There was no difference by region in the barriers identified in the focus group workshops; however, the proposed solutions to overcoming the barriers were specific to each site.The four-step process developed by the ECOG and the NMA used the focus group methodology to identify and overcome barriers to participation of African Americans in cancer clinical trials. Outreach efforts to educate patients, their families, and community physicians about cancer clinical trials should be directed at overcoming patient suspicions and providing practical information to physicians about specific trials and how to enroll patients.

Abstract

Current diagnostic methods for head and neck metastasis are limited for monitoring recurrence and assessing oxygenation. 1H MR spectroscopy (1H MRS) provides a noninvasive means of determining the chemical composition of tissue and thus has a unique potential as a method for localizing and characterizing cancer. The purposes of this investigation were to measure 1H spectral intensities of total choline (Cho), creatine (Cr), and lactate (Lac) in vivo in human lymph node metastases of head and neck cancer for comparison with normal muscle tissue and to examine relationships between metabolite signal intensities and tissue oxygenation status.Volume-localized Lac-edited MRS at 1.5 T was performed in vivo on the lymph node metastases of 14 patients whose conditions were untreated and who had primary occurrences of squamous cell carcinoma. MRS measurements were acquired also from the neck muscle tissue of six healthy volunteers and a subset of the patients. Peak areas of Cho, Cr, and Lac were calculated. Tissue oxygenation (pO2) within the abnormal lymph nodes was measured independently using an Eppendorf polarographic oxygen electrode.Cho:Cr ratios were significantly higher in the nodes than in muscle tissue (node Cho:Cr = 2.9 +/- 1.6, muscle Cho:Cr = 0.55 +/- 0.21, P = .0006). Lac was significantly higher in cancer tissue than in muscle (P = .01) and, in the nodes, showed a moderately negative correlation with median pO2 (r = -.76) over a range of approximately 0 to 30 mm Hg. Nodes with oxygenation values less than 10 mm Hg had approximately twice the Lac signal intensity as did nodes with oxygenation values greater than 10 mm Hg (P = .01). Cho signal intensity was not well correlated with pO2 (r = -.46) but seemed to decrease at higher oxygenation levels (>20 mm Hg).1H MRS may be useful for differentiating metastatic head and neck cancer from normal muscular tissue and may allow for the possibility of assessing oxygenation. Potential clinical applications include the staging and monitoring of treatment.

Abstract

Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

Abstract

Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma.Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy).All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases.Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.

Abstract

The importance of hypoxia in limiting the sensitivity of tumor cells to ionizing radiation has long been known.We evaluated the tissue oxygenation status with a polarographic needle electrode system in 37 patients with malignancies of the head and neck and correlated the pO2 of 25 patients with treatment outcome.Sixteen tumors contained areas of severe hypoxia, defined by pO2 values below 2.5 mm Hg. Tumor oxygenation parameters were not correlated with hemoglobin, age, and history of tobacco use. There were no subcutaneous PO2 values below 10 mm Hg (ie, no areas of moderate or severe hypoxia), whereas this degree of hypoxia was commonly found in the tumors. Though not statistically significant, hypoxic tumors showed trends for poorer treatment outcome.Our data demonstrate a great interindividual variability in the oxygenation of head and neck cancers and appears unassociated with clinical parameters. The method is capable of identifying patients with poorly oxygenated tumors, thereby providing important information for selecting patients who might need customized therapy designed to kill hypoxic tumor cells. Hypoxic tumors show a consistent trend for poor treatment outcome.

Abstract

Minority accrual onto clinical trials is of significant interest to cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG) conducted a study to identify barriers and solutions to African American accrual onto clinical trials.We hypothesize that the National Medical Association (NMA) might provide insight into ways to increase minority participation and that ECOG might facilitate that participation. Four sites were selected in which NMA chapters existed and ECOG main institutions with less than half of the corresponding percentage of minorities in their communities entered trials for 1992. Fifteen workshops were conducted using discussions and open-ended, self-administered questionnaires.Seventy percent of NMA physicians cited mistrust of the research centers, fear of losing patients, and a lack of respect from ECOG institutions as the most important barriers to minority cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine percent of NMA and 43% of ECOG physicians cited a lack of information about specific trials. Nearly half of NMA physicians (47%) cited a lack of minority investigators as a barrier, compared with 4% of ECOG physicians. Solutions by both groups were improved communication (73%) and culturally relevant educational materials (40%). ECOG physicians cited more minority outreach staff as a potential solution (22% v 6%). NMA physicians cited increased involvement of referring physicians (44% v4%).NMA physicians who serve a significant sector of the African American population demonstrated a willingness to participate and work with a cooperative group effort to increase participation of minority patients and investigators.

Abstract

Considerable evidence exists to suggest that tumor hypoxia results in radioresistance. Historically, it has been difficult to assess tumor oxygen tension levels reliably. These levels can now be assessed in head and neck malignancies using the Eppendorf pO2 histograph, which uses a fine-needle electrode and a computerized micromanipulator. This technology was used to compare the pretreatment tumor oxygen tension level in lymph node metastases of patients with head and neck cancer to measurements taken during nonsurgical treatment after a partial response had been achieved.Prospective study.Oxygen tension levels were measured in the cervical lymph nodes of 10 patients with biopsy-proven head and neck squamous cell carcinoma and cervical metastases who were being treated with nonsurgical management. These levels were obtained using the Eppendorf pO2 histograph system. Measurements were taken before the start of treatment and were repeated when the size of the cervical metastatic node had decreased by 50%. Normal subcutaneous tissue was measured during the same session. The mean and median pO2 levels, as well as the percentage of measurements with pO2 less than 5 mm Hg were determined.A mean of 72.6 measurements per session was taken from each lymph node. The median tumor pO2 measurement fell from a mean (+/-SD) of 13.9+/-8.0 mm Hg to 7.3+/-9.9 mm Hg. Even more dramatic, however, was the substantial increase in the percentage of values less than 5 mm Hg, a rise from 29% to 52%.While there is variability both in the pretreatment oxygenation of head and neck cervical metastases and in the change in tumor oxygen tension during treatment, there appears to be a decrease in the overall oxygenation of the tumors. The dramatic increase in very low oxygen measurements may reflect selective survival of radioresistant or chemoresistant hypoxic tumor cells. Cells at the very low level would be expected to be radiobiologically hypoxic (resistant to radiation-induced cell kill).

Abstract

The use of chemotherapy and irradiation for organ preservation attempts to eliminate the need for extensive surgery in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). We sought to characterize the morbidity of surgery in patients who needed surgery after treatment with induction chemotherapy followed by simultaneous chemotherapy and radiotherapy (chemoradiotherapy). The surgical morbidity within the first 30 postoperative days of 17 patients treated in an organ preservation approach between July 1991 and December 1994 was compared with a control group of patients undergoing similar surgical procedures during the same period. The organ preservation study patients underwent surgical procedures consisting of 18 neck dissections and 5 resections of the primary site. Six patients in the organ preservation study group experienced 8 surgical complications within the first 30 postoperative days, and most complications were minor. There was no significant difference in the duration of surgery or length of hospitalization between study patients and matched controls. Our surgical complication rate (35.3%) was higher but not statistically different from that of the control group, and compared favorably to reports of surgical morbidity (44% to 61%) in the literature on patients treated with chemoradiotherapy. The lower complication rate seen in this study may be a reflection of early surgical intervention as part of our organ preservation study scheme, the preponderance of neck dissections performed, and the limited number of pharyngeal procedures performed.

CHEMOTHERAPY FOR RECURRENT AND METASTATIC HEAD AND NECK-CANCERHEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICAPinto, H. A., Jacobs, C.1991; 5 (4): 667-686

Abstract

At the present time, the treatment of recurrent and metastatic head and neck squamous and salivary gland cancers with chemotherapy is palliative. Pain relief, improvement in functional parameters, and improved survival are important goals. Although survival benefits are small, palliation can be significant. For squamous cancers, the median duration of response to chemotherapy is 2 to 4 months, and overall survival is about 6 months. Responses can be achieved with acceptable toxicity for good palliation in approximately 30% of patients treated with the standard regimens. Although more intensive chemotherapy regimens often result in higher response rates in pilot trials, they do not offer significant gains in effectiveness or survival. In salivary gland malignancies, results are substantially better, but this may only reflect the different natural history of this heterogeneous group of tumors. A small number of patients will have excellent and very durable responses to chemotherapy. Unfortunately, at this time we are unable to select these patients or determine which regimen will produce this desired result. The optimal use of currently available drugs is in the process of refinement. The timing of palliative chemotherapy represents a major challenge to oncologists and patients. Chemotherapy may in the future have a role in the cure of patients with recurrent disease, but innovative therapy, combined modality approaches, and new drug development will all need to be investigated. We look forward toward a new understanding of tumor biology and the development of agents that may substantially improve the control of these tumors.